S-phase fraction as a useful marker for prognosis and therapeutic response in patients with aplastic anemia
Anil Kumar Tripathi, Payal Tripathi, Ashutosh Kumar, Rizwan Ahmad, Raj K. Singh, Anil K. Balapure, Achchhe L. Vishwakerma
2008
Hematology/Oncology and Stem Cell Therapy
A plastic anemia (AA) is a potentially lifelthreatl l ening failure of hematopoiesis characterized by pancytopenia and bone marrow aplasia. 1 Patients with aplastic anemia have a stem cell defect both in proliferation and differentiation as shown by longlterm bone marrow culture, longlterm cell assays and committed progenitor assays. 2 Patients with AA have an increased risk of developing clonal hematologil l cal diseases including paroxysmal nocturnal hemoglol l binuria (PNH), myelodysplastic
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... yndrome (MDS) or acute myeloid leukemia (AML). 3,4 The evolution from AA to MDS/AML is marked with increased proliferal l tive activity with or without development of cytogenetic abnormalities. Around 10% to 20% of survivors of AA BACKGROUnD: the functional definition of aplastic anemia (aa) is the failure of hematopoietic stem cells to proliferate. the aim of the present study was to analyze the s-phase fraction (spf) (proliferative activity) in pa-tients with aa at diagnosis to explore its relationship with disease characteristics and its value in discriminating among patients with different prognoses. We also investigated whether the spf value influenced the response to immunosuppressive therapy in aa patients. PATIenTS AnD MeThODS: the analysis of spf at the time of diagnosis was carried out by flow cytometry on peripheral blood samples from 53 consecutive patients with aa and 30 age-and sex-matched controls. all pa-tients were given cyclosporine and followed up periodically to determine response to therapy. ReSULTS: based on the median spf, aa patients were divided into two groups: patients with spf ≤0.59% (n=27) and patients with spf >0.59% (n=26). an spf >0.59% was associated with advanced age (P=.02) and elevated serum ldh level (P=.01). patients with an spf >0.59% also had a higher incidence of paroxysmal nocturnal hemoglobinuria and cytogenetic abnormalities. during a median follow-up of 18 months, 3.7% of patients with spf ≤0.59 and 11.5% of patients with spf >0.59% developed dysplasia and one patient with spf >0.59% con-verted into aml. a significantly higher (P=.018) overall response rate of 53.9% was found in patients with spf >0.59% versus 22.2% of patients with spf ≤0.59% at 6 months. COnCLUSIOnS: independently of the peripheral blood count, the spf at diagnosis may provide information on the expected response to immunosuppressive therapy and the propensity for disease to evolve into mds/aml. hence, spf may serve as an early indicator for the evolution of mds/aml in patients with aa and thus contrib-ute to therapeutic decisions. from the a departments of medicine, b pathology, and c biochemistry, csm medical university and the d central drug research institute, lucknow, uttar pradesh, india correspondence: anil Kumar tripathi, md · department of medicine, csm medical university, shahmeena road, chowk, lucknow, uttar pradesh, india · t:
doi:10.1016/s1658-3876(08)50007-0
pmid:20058476
fatcat:3owbvggkrvfbzkcygxrnajb4hu